1. The Y238X stop codon polymorphism in the human β-glucan receptor dectin-1 and susceptibility to invasive aspergillosis.
- Author
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Chai LY, de Boer MG, van der Velden WJ, Plantinga TS, van Spriel AB, Jacobs C, Halkes CJ, Vonk AG, Blijlevens NM, van Dissel JT, Donnelly PJ, Kullberg BJ, Maertens J, and Netea MG
- Subjects
- Adult, Belgium, Case-Control Studies, Cytokines, Female, Flow Cytometry, Gene Frequency, Genotype, Hematopoietic Stem Cell Transplantation adverse effects, Heterozygote, Humans, Lectins, C-Type, Male, Membrane Proteins metabolism, Middle Aged, Nerve Tissue Proteins metabolism, Netherlands, Polymorphism, Single Nucleotide, beta-Glucans metabolism, Aspergillosis genetics, Aspergillosis immunology, Codon, Terminator genetics, Genetic Predisposition to Disease genetics, Membrane Proteins genetics, Nerve Tissue Proteins genetics
- Abstract
Background: Dectin-1 is the major receptor for fungal β-glucans on myeloid cells. We investigated whether defective Dectin-1 receptor function, because of the early stop codon polymorphism Y238X, enhances susceptibility to invasive aspergillosis (IA) in at-risk patients., Methods: Association of Dectin-1 Y238X polymorphism with occurrence and clinical course of IA was evaluated in 71 patients who developed IA post hematopoietic stem cell transplantation (HSCT) and in another 21 non-HSCT patients with IA. The control group consisted of 108 patients who underwent HSCT. Functional studies were performed to investigate consequences of the Y238X Dectin-1 polymorphism., Results: The Y238X allele frequency was higher in non-HSCT patients with IA (19.0% vs 6.9%-7.7%; P < .05). Heterozygosity for Y238X polymorphism in HSCT recipients showed a trend toward IA susceptibility (odds ratio, 1.79; 95% CI, .77-4.19; P = .17) but did not influence clinical course of IA. Functional assays revealed that although peripheral blood mononuclear cells with defective Dectin-1 function due to Y238X responded less efficiently to Aspergillus, corresponding macrophages showed adequate response to Aspergillus., Conclusions: Dectin-1 Y238X heterozygosity has a limited influence on susceptibility to IA and may be important in susceptible non-HSCT patients. This is partly attributable to redundancy inherent in the innate immune system. Larger studies are needed to confirm these findings.
- Published
- 2011
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